Zymosan-activated plasma-mediated thromboxane production by the perfused rabbit liver and isolated hepatocytes: involvement of calcium.
The present study investigates the mechanism of zymosan-activated plasma (ZAP)-mediated eicosanoid production by the isolated, perfused rabbit liver and described ZAP-mediated eicosanoid stimulation in cultured hepatocytes. Perfused livers receiving untreated plasma demonstrated no significant changes in portal venous pressure or the rates of release of lactic dehydrogenase or acid phosphatase activity (indicators of cellular injury). The control group livers demonstrated stable rates of release for 6-keto PGF1 alpha and thromboxane B2 (TXB2). In contrast, the infusion of ZAP alone resulted in a rapid but transient release of TXB2 from the livers. No significant changes in perfusion pressure or enzyme release were observed following ZAP administration. Perfusion of livers with a calcium-free buffer decreased the basal rates of both 6-keto PGF1 alpha and TXB2 production and significantly, but not completely, attenuated the ZAP-mediated increase in hepatic TXB2 production. Perfusion of livers with nifedipine (3 microM) had no effect on ZAP-mediated TXB2 production in this model. Isolated hepatocytes responded to ZAP-treatment with significant increases in TXB2 production. These data suggest that activated fluid phase complement components induce thromboxane production by specific cells within the liver and that this stimulation is partially dependent upon the release of intracellular calcium but independent of complement-mediated cellular injury.
Flynn
J T
JT
Department of Physiology, Thomas Jefferson University, Philadelphia, PA 19107.
Hellerman
P
P
Shelly
M A
MA
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001769:Blood; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis*; D015054:Zymosan / Q000494:pharmacology*
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015054:Zymosan; D007770:L-Lactate Dehydrogenase; D000135:Acid Phosphatase; D009543:Nifedipine; D002118:Calcium